A Trial of Neuroprotection With ACTH in Acute Optic Neuritis — ACTHAR  

Multiple Sclerosis Clinical Trial

Official title: A Phase IV Trial of Neuroprotection With ACTH in Acute Optic Neuritis

Status Terminated

Clinical Trial Summary

We hypothesize that the novel melanocortin-mediated anti-inflammatory effects of ACTH will reduce axonal loss following ON by limiting inflammatory optic nerve injury. We will compare the effect of ACTH and intravenous methylprednisolone therapy on axonal injury following ON using OCT, a sensitive, reproducible and noninvasive tool to measure RNFL thickness.

The primary outcome will be the average RNFL thickness at 6 months. Additional pre-specified statistical analyses will compare the difference in the mean RNFL thickness at 6 months in the affected eye between the IV methylprednisolone- and Acthar-treated groups, and the mean 6-month affected eye RNFL thicknesses adjusted for the baseline unaffected eye RNFL. The secondary outcome measure will examine the frequency of optic nerves with RNFL swelling between the IV methylprednisolone- and Acthar-treated groups at 1 and 3 months. A predefined exploratory outcome will compare the ganglion cell plus inner plexiform layer (GC+IPL) thickness at 6 months between treatment groups. Additional tertiary outcome will be the assessment of changes in fatigue, mood, visual function depression, and quality of life in patients with AON. Assessment will be completed by administration of the following questionnaires: Modified Fatigue Impact Scale, Multiple Sclerosis Quality of Life 54 Instrument, 25-item Visual Function Questionnaire with 10-item supplement, Beck's Depression Inventory. These questionnaires have been validated for the MS (AON) population. Descriptive and correlative analysis will be done at each visit time point to assess for QOL for this study population.

Clinical Trial Description

Patients with their first episode of unilateral acute ON will be treated with either 3 days of IV methylprednisolone followed by 11 days of oral prednisone or 15 days of intramuscular or subcutaneous corticotropin (Acthar).

This is a parallel active group, randomized controlled trial in which up to 100 people with clinically unilateral acute optic neuritis (≤ 2 weeks of vision loss; with or without a previous diagnosis of relapsing remitting MS) will be treated with either ACTH or IV methylprednisolone/prednisone for 2 weeks to assess RNFL thickness. The primary, secondary, and tertiary outcomes will be as noted above. Participants will be assessed for inclusion/exclusion criteria by their treating neurologist/ophthalmologist at the University of Colorado Denver (PI- Dr. Jeffrey Bennett) or The University of Pennsylvania Scheie Eye Institute (PI- Dr. Kenneth Shindler). Following informed consent, the University of Colorado will determine patient randomization for both sites per the established randomization scheme. A secured fax or email confirmation regarding randomization will be sent to the University of Pennsylvania research staff and proper pharmacy orders will be placed by the site investigator or designee. We expect to enroll up to 50 subjects per institution.

Following informed consent and randomization, participants will undergo baseline procedures (visit 1) and receive treatment with either high dose methylprednisolone (1000 mg IV qD for 3 days followed by 60 mg oral prednisone daily for 11 days) or Acthar (80 U IM or SC daily for 5 days followed by 40 U IM or SC daily for 10 days). Study follow-up visits will subsequently occur at 1, 3, and 6 months. During each visit, including baseline (visit 1), ETDRS, low contrast acuity (2.5%), and color vision (Farnsworth D-15) will be assessed. OCT evaluations (Optic Disc Cube 200x200 and Macular Cube 512x128) will be performed at baseline, 1, 3 and 6 months using spectral domain OCT (Cirrus OCT; Carl Zeiss Meditec, Dublin, CA, USA). Automated visual fields (Humphrey 30-2 SITA) will be performed at baseline (visit 1) and month 6. Modified Fatigue Impact Scale, Multiple Sclerosis Quality of Life 54 Instrument, 25-item Visual Function Questionnaire with 10-item supplement, Beck's Depression Inventory questionnaires will be assessed at each study visit. The patient's treating physician will perform blood tests and MRI evaluations to exclude other causes of optic neuropathy at the initial study visit as part of their routine care.

RNFL edema will be defined as either average RNFL thickness greater than the 95th percentile of the age matched normal database or a ratio of RNFL thickness (affected/fellow eye) greater than 1.1 in any quadrant.8 The study sites will collect and report data on AEs and SAEs per standard practice.

Detailed Patient Schedule of Assessments:

Baseline, within 2 weeks of onset of vision loss (approximately 2 hours):

• Consent and Discussion of Study Expectations

• Eligibility Checklist

• Review of Medical History & Demographics

• Record list of Con Meds, Co-Morbidities, and Symptoms at time of Diagnosis

• Obtain Randomization Number

• Administer MFIS, BDI, VFQ-25 and 10-item supplement, and MSQOL-54 questionnaires

• Eye Testing (OCT - [Optic Disc Cube 200x200 and Macular Cube 512x128], Visual Acuity [High Contrast ETDRS], Low-contrast Letter Acuity [Sloan 2.5% and 1.25% letters], Color Vision [Farnsworth D15], Humphrey's visual fields (HVF).

• Administer Study Medication (either IM or SC Acthar Gel or IV Methylprednisolone with oral taper)

• Labs and MRI, per standard of care

Month 1 +/- 3 days (approximately 1.5 hours):

• Review of AEs and Con Meds

• Administer MFIS, BDI, VFQ-25 and 10-item supplement, and MSQOL-54 questionnaires

• Eye Testing (OCT - [Optic Disc Cube 200x200 and Macular Cube 512x128], Visual Acuity [High Contrast ETDRS], Low-contrast Letter Acuity [Sloan 2.5% and 1.25% letters], Color Vision [Farnsworth D15]

Month 3 +/- 3 days (approximately 1.5 hours):

• Review of AEs and Con Meds

• Administer MFIS, BDI, VFQ-25 and 10-item supplement, and MSQOL-54 questionnaires

• Eye Testing (OCT - [Optic Disc Cube 200x200 and Macular Cube 512x128], Visual Acuity [High Contrast ETDRS], Low-contrast Letter Acuity [Sloan 2.5% and 1.25% letters], Color Vision [Farnsworth D15]

Month 6 +/- 3 days (approximately 2 hours):

• Review of AEs and Con Meds

• Administer MFIS, BDI, VFQ-25 and 10-item supplement, and MSQOL-54 questionnaires

• Eye Testing (OCT - [Optic Disc Cube 200x200 and Macular Cube 512x128], Visual Acuity [High Contrast ETDRS], Low-contrast Letter Acuity [Sloan 2.5% and 1.25% letters], Color Vision [Farnsworth D15], Humphrey's visual fields (HVF) ;

Related Conditions & MeSH terms

• Multiple Sclerosis
• Neuritis
• Optic Neuritis

• NCT number: NCT01838174
• Study type: Interventional
• Source: University of Colorado, Denver
• Status: Terminated
• Phase: Phase 4
• Start date: May 2013
• Completion date: January 13, 2022